Valproic acid attenuates inflammation in experimental autoimmune neuritis.
Valproic acid (VPA) is a short-chain branched fatty with anti-inflammatory, neuro-protective and axon-remodeling effects. We investigated the effects of VPA in rats in which experimental autoimmune neuritis (EAN) had been induced (EAN rats). VPA (300 mg/kg, intraperitoneally) administration to EAN rats once daily immediately following immunization significantly suppressed mRNA levels of interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-4, IL-6 and IL-17 in the lymph nodes of EAN rats. In peripheral blood and sciatic nerves of EAN rats, Foxp3(+) cells were increased but IL-17(+) cells were decreased during VPA treatment. Furthermore, suppressive and therapeutic treatment with VPA greatly attenuated both accumulation of macrophages, T cells and B cells, and demyelination in sciatic nerves, and greatly reduced the severity and duration of EAN. In summary, our data demonstrated that VPA could effectively suppress inflammation in EAN, suggesting that VPA could be a potent candidate for treatment of autoimmune neuropathies.
Zhang
Z
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Institute of Brain Research, University of Tuebingen, Germany. zhangzhiren@yahoo.com
Zhang
Z Y
ZY
Fauser
U
U
Schluesener
H J
HJ
D000818:Animals; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D009444:Neuritis, Autoimmune, Experimental / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D014635:Valproic Acid